Advanced search
1 file | 1.51 MB

Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic inflammation in mice

(2015) EUROPEAN JOURNAL OF IMMUNOLOGY. 45(10). p.2898-2910
Author
Organization
Abstract
Plakophilin-3 (PKP3) is a member of the armadillo protein family, which is important in cell-cell contacts and signaling during development and tumorigenesis. In conventional facilities, PKP3-deficient mice (PKP3(-/-)) develop spontaneous dermatitis, indicating a possible involvement of PKP3 in inflammatory responses. Here, we show that PKP3 deficiency sensitizes mice to irritant contact dermatitis induced by phorbol myristate acetate (PMA). This sensitization occurred in mice with PKP3 deficiency in the hematopoietic system (PKP3(-/-hem)), but not if the deficiency was specific to skin keratinocytes (PKP3(-/-ker)). In a model of dextran sulfate sodium induced colitis, ubiquitous PKP3 deletion, but not intestinal epithelial PKP3 deficiency (PKP3(-/-IEC)), impaired survival from disease. Interestingly, PKP3(-/-hem) mice also displayed increased sensitivity to dextran sulfate sodium induced colitis. Finally, PKP3(-/-) mice were more sensitive to the lethality of lipopolysaccharide (LPS) injection than wild-type (WT) mice, and this phenotype was associated with increased intestinal permeability. PKP3(-/-IEC) mice did not reproduce the enhanced endotoxin reactivity of PKP3(-/-) mice, in contrast to PKP3(-/-hem) mice. Finally, in vitro stimulation of WT neutrophils with LPS or PMA increased Pkp3 expression. In conclusion, our data highlight a novel role for hematopoietic PKP3 in the regulation of both locally and systemically induced immune responses. Nonetheless, further research is needed to unravel the underlying mechanism.
Keywords
Dermatitis, Hematopoietic cell, Colitis, Acute inflammation, Intestine, Plakophilin-3, Sepsis, Skin, CRE-MEDIATED RECOMBINATION, RNA-BINDING PROTEINS, IN-VIVO, INTESTINAL INFLAMMATION, ATOPIC-DERMATITIS, EPITHELIAL-CELLS, BARRIER FUNCTION, TRAUMA PATIENTS, INJURY, GUT

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.51 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Sklyarova, Tatyana, Jolanda van Hengel, Elien Van Wonterghem, Claude Libert, Frans Van Roy, and Roosmarijn Vandenbroucke. 2015. “Hematopoietic Plakophilin-3 Regulates Acute Tissue-specific and Systemic Inflammation in Mice.” European Journal of Immunology 45 (10): 2898–2910.
APA
Sklyarova, T., van Hengel, J., Van Wonterghem, E., Libert, C., Van Roy, F., & Vandenbroucke, R. (2015). Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic inflammation in mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 45(10), 2898–2910.
Vancouver
1.
Sklyarova T, van Hengel J, Van Wonterghem E, Libert C, Van Roy F, Vandenbroucke R. Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic inflammation in mice. EUROPEAN JOURNAL OF IMMUNOLOGY. 2015;45(10):2898–910.
MLA
Sklyarova, Tatyana, Jolanda van Hengel, Elien Van Wonterghem, et al. “Hematopoietic Plakophilin-3 Regulates Acute Tissue-specific and Systemic Inflammation in Mice.” EUROPEAN JOURNAL OF IMMUNOLOGY 45.10 (2015): 2898–2910. Print.
@article{6973767,
  abstract     = {Plakophilin-3 (PKP3) is a member of the armadillo protein family, which is important in cell-cell contacts and signaling during development and tumorigenesis. In conventional facilities, PKP3-deficient mice (PKP3(-/-)) develop spontaneous dermatitis, indicating a possible involvement of PKP3 in inflammatory responses. Here, we show that PKP3 deficiency sensitizes mice to irritant contact dermatitis induced by phorbol myristate acetate (PMA). This sensitization occurred in mice with PKP3 deficiency in the hematopoietic system (PKP3(-/-hem)), but not if the deficiency was specific to skin keratinocytes (PKP3(-/-ker)). In a model of dextran sulfate sodium induced colitis, ubiquitous PKP3 deletion, but not intestinal epithelial PKP3 deficiency (PKP3(-/-IEC)), impaired survival from disease. Interestingly, PKP3(-/-hem) mice also displayed increased sensitivity to dextran sulfate sodium induced colitis. Finally, PKP3(-/-) mice were more sensitive to the lethality of lipopolysaccharide (LPS) injection than wild-type (WT) mice, and this phenotype was associated with increased intestinal permeability. PKP3(-/-IEC) mice did not reproduce the enhanced endotoxin reactivity of PKP3(-/-) mice, in contrast to PKP3(-/-hem) mice. Finally, in vitro stimulation of WT neutrophils with LPS or PMA increased Pkp3 expression. In conclusion, our data highlight a novel role for hematopoietic PKP3 in the regulation of both locally and systemically induced immune responses. Nonetheless, further research is needed to unravel the underlying mechanism.},
  author       = {Sklyarova, Tatyana and van Hengel, Jolanda and Van Wonterghem, Elien and Libert, Claude and Van Roy, Frans and Vandenbroucke, Roosmarijn},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keyword      = {Dermatitis,Hematopoietic cell,Colitis,Acute inflammation,Intestine,Plakophilin-3,Sepsis,Skin,CRE-MEDIATED RECOMBINATION,RNA-BINDING PROTEINS,IN-VIVO,INTESTINAL INFLAMMATION,ATOPIC-DERMATITIS,EPITHELIAL-CELLS,BARRIER FUNCTION,TRAUMA PATIENTS,INJURY,GUT},
  language     = {eng},
  number       = {10},
  pages        = {2898--2910},
  title        = {Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic inflammation in mice},
  url          = {http://dx.doi.org/10.1002/eji.201445440},
  volume       = {45},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: